What is the recommended treatment for an acute gout attack and subsequent long‑term urate‑lowering therapy?

Gout Treatment: Acute Flares and Long-Term Urate-Lowering Therapy

Acute Gout Attack Management

For an acute gout flare, initiate treatment within 24 hours using NSAIDs, low-dose colchicine, or corticosteroids as equally effective first-line options, selecting based on renal function, cardiovascular risk, and gastrointestinal comorbidities. 1

First-Line Monotherapy Options

NSAIDs:

• Use full FDA-approved anti-inflammatory doses (naproxen, indomethacin, or sulindac) and continue at full dose until complete resolution of the attack. 1
• Indomethacin offers no superiority over other NSAIDs despite traditional preference. 1
• Contraindications: Severe renal impairment (eGFR <30 mL/min), heart failure, cirrhosis, active peptic ulcer disease, or anticoagulation therapy. 1, 2

Low-Dose Colchicine:

• Dosing regimen: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (total 1.8 mg). 1, 3
• This low-dose protocol achieves equivalent efficacy to high-dose regimens (1.2 mg followed by 0.6 mg hourly for 6 hours) but with significantly fewer gastrointestinal adverse effects. 1
• Critical timing: Must be initiated within 36 hours of symptom onset; efficacy declines sharply beyond this window. 1, 4
• Absolute contraindications: Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially in patients with renal or hepatic impairment—this combination can cause fatal toxicity. 1, 4, 3
• Renal dosing: Avoid entirely in severe renal impairment (CrCl <30 mL/min). 4, 3

Corticosteroids:

• Oral prednisone: 0.5 mg/kg/day (approximately 30–35 mg daily) for 5–10 days at full dose then stop, or 2–5 days at full dose followed by 7–10 day taper. 1, 2
• Preferred in: Severe renal impairment, cardiovascular disease, heart failure, cirrhosis, peptic ulcer disease, or when NSAIDs/colchicine are contraindicated. 1, 2
• Intramuscular option: Triamcinolone acetonide 60 mg IM for patients unable to take oral medications. 1, 2
• Intra-articular injection: For monoarticular or oligoarticular involvement of accessible large joints (dose varies by joint size: knee ~40 mg, ankle 20–30 mg). 1, 2
• Contraindications: Systemic fungal infections, uncontrolled diabetes. 1, 2

Combination Therapy for Severe Attacks

For polyarticular gout (≥4 joints) or severe attacks with multiple large joints involved, initiate combination therapy: 1, 4

• Colchicine + NSAID
• Oral corticosteroid + colchicine
• Intra-articular steroid + any oral agent

Avoid: NSAIDs combined with systemic corticosteroids due to synergistic gastrointestinal toxicity. 4

Monitoring Treatment Response

Define inadequate response as: <20% pain improvement within 24 hours OR <50% improvement at ≥24 hours. 1, 2

If inadequate response occurs: Switch to alternative monotherapy or add a second agent; consider alternative diagnoses including septic arthritis. 1, 2

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Long-Term Urate-Lowering Therapy (ULT)

Indications for Initiating ULT

Do NOT initiate ULT after a first gout attack or in patients with infrequent attacks (<2 per year). 1

Strongly recommend initiating ULT in patients with: 4

• Recurrent gout (≥2 episodes per year)
• Subcutaneous tophi
• Radiographic joint damage from gout
• Chronic kidney disease stage ≥3
• Urolithiasis

Conditionally recommend ULT for: 4

• Patient preference for early intervention
• Young age at disease onset
• Serum urate >9 mg/dL (>476 µmol/L)

Shared Decision-Making Discussion

Before initiating ULT, discuss with patients: 1

• Benefits: Reduced flare frequency after 12 months (not within first 6 months)
• Harms: Rash with allopurinol; abdominal pain, diarrhea, musculoskeletal pain with febuxostat
• Costs: Generic allopurinol is least expensive
• Need for concomitant prophylaxis during initiation

First-Line ULT: Allopurinol

Initiation and titration strategy: 4, 5

• Start low: 100 mg daily (50–100 mg in CKD)
• Titrate slowly: Increase by 100 mg every 2–4 weeks
• Target: Serum urate <6 mg/dL (<0.36 mmol/L)
• Maximum dose: 800 mg daily 5

Renal dosing adjustments: 5

• CrCl 10–20 mL/min: 200 mg daily maximum
• CrCl <10 mL/min: 100 mg daily maximum
• CrCl <3 mL/min: Lengthen dosing interval

Alternative: Febuxostat 1

• Febuxostat 40 mg/day and allopurinol 300 mg/day are equally effective at lowering serum urate. 1
• Consider in allopurinol-allergic patients or those with inadequate response.

Mandatory Prophylaxis During ULT Initiation

Provide anti-inflammatory prophylaxis for at least 6 months when starting or adjusting ULT to prevent acute flares. 1, 4

First-line prophylaxis options: 1, 4

• Low-dose colchicine: 0.6 mg once or twice daily
• Low-dose NSAID: Naproxen 250 mg twice daily (with PPI if indicated)

Second-line prophylaxis (if colchicine/NSAIDs contraindicated): 1, 2

• Low-dose prednisone: <10 mg/day
• Duration: Continue for 3–6 months, or 3 months after achieving target serum urate if no tophi present, or 6 months after target if tophi present. 4

High-quality evidence shows prophylaxis beyond 8 weeks is more effective than shorter durations. 1

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Critical Management Principles

Do NOT Interrupt Ongoing ULT During an Acute Flare

Continue allopurinol or febuxostat during acute gout attacks if the patient is already on ULT. 1, 2, 4

Common Pitfalls to Avoid

• Delaying acute treatment beyond 24 hours markedly reduces efficacy of all therapies. 1, 2, 4
• Starting allopurinol at 300 mg daily increases flare risk and hypersensitivity reactions; always start at ≤100 mg and titrate. 4, 5
• Using high-dose colchicine regimens (>1.8 mg in first hour) provides no additional benefit but substantially increases gastrointestinal toxicity. 1, 4
• Omitting prophylaxis when initiating ULT dramatically increases acute flare risk in the first 6 months. 1, 4
• Using high-dose prednisone (>10 mg/day) for prophylaxis is inappropriate and increases long-term corticosteroid complications. 2, 4

Drug Interaction Alert

Fatal colchicine toxicity has been reported with strong CYP3A4/P-gp inhibitors (clarithromycin, verapamil, cyclosporine, ketoconazole, ritonavir). This combination is absolutely contraindicated, especially in renal or hepatic impairment. 1, 4, 3